Subjective Social Isolation and Sleep Disturbances: Inflammatory Mechanisms in Ag

描述(申请人提供)：与社会隔绝的老年人全因死亡的风险增加，以及几种特定的传染病、肿瘤和心血管疾病。然而，这些效应的神经生物学和基因组机制在很大程度上仍未被探索。我们的初步研究发现，主观的社交隔离与睡眠障碍以及炎症标志物的增加有关。这项研究的总体目标是评估老年人的主观社会隔离，以及这种社会隔离对睡眠的动态平衡调节和炎症生物动力学的影响。鉴于我们的发现，炎症标志物的细胞和基因组激活伴随着主观的社交隔离和睡眠障碍，这项研究将测试自然睡眠和实验性睡眠不足对社交孤立老年人和社交融合型老年人的社会连接感和细胞和基因组炎症标志物的影响。这项研究的目的是：1)确定社会孤立老年人睡眠障碍的性质和严重程度；2)评估社会孤立老年人炎症的细胞和基因组标志物；以及3)检查睡眠不足和恢复睡眠对社会孤立老年人的行为症状和炎症细胞和基因组标志物的贡献。在观察和实验研究设计的框架内，理解社会孤立对睡眠的动态平衡调节的影响，对于确定可能推动社会孤立与健康之间联系的心理生物学途径具有重要意义。鉴于睡眠不足会导致促炎细胞因子活性升高，睡眠和细胞因子之间双向关系的失调可能会导致一个前馈循环，在这个循环中，睡眠中断和促炎细胞因子升高会造成恶性循环，加剧睡眠，并导致社会疏离感。这项研究的结果对于开发针对睡眠障碍的干预措施具有直接的临床意义，这些干预措施可能会对主观上与世隔绝的老年人的发病率和结局产生影响。 公共卫生相关性：社交隔离对老年人的健康有重大影响，但尚不清楚孤独感和情感联系的丧失如何导致疾病风险增加。鉴于我们的证据表明，社交隔离与睡眠障碍有关，而且这种睡眠困难会增加炎症，从而导致包括心血管疾病、糖尿病和癌症在内的许多医学疾病，这项研究将研究社交隔离、睡眠障碍和炎症之间的关系。这项研究将为开发针对睡眠障碍的潜在治疗方法提供信息，并可能预防处于社会孤立状态的老年人的疾病后果。

DESCRIPTION (provided by applicant): Older adults who are socially isolated have increased risk of all-cause mortality, and several specific infectious, neoplastic, and cardiovascular diseases. However, the neurobiologic and genomic mechanisms of these effects remain largely unexplored. Our preliminary studies have found that subjective social isolation is associated with sleep disturbance as well as increases in markers of inflammation. The over-arching objective of this study is to evaluate subjective social isolation in older adults and the consequences of such social isolation for the homeostatic regulation of sleep and inflammatory biology dynamics. Given our findings that cellular and genomic activation of inflammatory markers occurs along with subjective social isolation as well as sleep disturbance, this study will test the consequences of naturalistic and experimental sleep loss on feelings of social connection and cellular and genomic markers of inflammation in socially isolated vs. socially integrated older adults. The study aims are: 1) to determine the nature and severity of disordered sleep in socially isolated older adults; 2) to evaluate cellular and genomic markers of inflammation in socially isolated older adults; and 3) to examine the contribution of sleep loss and recovery sleep to behavioral symptoms and cellular and genomic markers of inflammation in socially isolated older adults. Understanding the consequences of social isolation for the homeostatic regulation of sleep within the framework of an observational and experimental research design has implications for identifying the psychobiological pathways that might drive the link between social isolation and health. Given that sleep loss induces elevations in proinflammatory cytokine activity, dysregulation of the bi-directional relationship between sleep and cytokines may result in a feed-forward loop in which disrupted sleep and elevated proinflammatory cytokines create a vicious cycle exacerbating sleep and contributing to feelings of social disconnection. Results of this study have immediate clinical implications for the development of interventions that target disordered sleep with potential effects on morbidity and outcomes in subjectively socially isolated older adults. PUBLIC HEALTH RELEVANCE: Social isolation has significant health consequences in older adults, but it is not known how feelings of loneliness and loss of emotional connections lead to increases in disease risk. Given our evidence that social isolation is associated with sleep disturbance, and such sleep difficulties increase inflammation with consequences for a number of medical disorders including cardiovascular disorder, diabetes mellitus, and cancer, this study will examine the relationships between social isolation, sleep disturbance and inflammation in socially isolated older adults. This study will inform the development of potential treatments that target disordered sleep with possible prevention of disease outcomes in older adults who are socially isolated.